Longitudinal analysis of hsa-miR-3163, hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-27a-3p as prognostic biomarkers in HIV-infected patients

MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of -identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-316...

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Published inFrontiers in immunology Vol. 16; p. 1565068
Main Authors Balkan, Ilker Inanç, Shahzadi, Andleeb, Sönmez, Haktan, Oktan, Burhaneddin, Umar, Muhammad Ihtisham, Mete, Bilgül, Tabak, Fehmi, Deniz, Günnur, Küçüksezer, Umut Can
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 06.05.2025
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ISSN1664-3224
1664-3224
DOI10.3389/fimmu.2025.1565068

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Abstract MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of -identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load). Blood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1 , 2 and 6 months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry. miR-27a-3p expression was significantly increased at 2 and 6 months of ART (p<0.001). miR-548ac-3p was upregulated at 6 month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265). Our findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.
AbstractList IntroductionMicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of in silico-identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load).MethodsBlood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1st, 2nd and 6th months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry.ResultsmiR-27a-3p expression was significantly increased at 2nd and 6th months of ART (p<0.001). miR-548ac-3p was upregulated at 6th month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756–0.9265).DiscussionOur findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.
MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of -identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load). Blood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1 , 2 and 6 months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry. miR-27a-3p expression was significantly increased at 2 and 6 months of ART (p<0.001). miR-548ac-3p was upregulated at 6 month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265). Our findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.
MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of in silico-identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load).IntroductionMicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of in silico-identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load).Blood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1st, 2nd and 6th months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry.MethodsBlood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1st, 2nd and 6th months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry.miR-27a-3p expression was significantly increased at 2nd and 6th months of ART (p<0.001). miR-548ac-3p was upregulated at 6th month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265).ResultsmiR-27a-3p expression was significantly increased at 2nd and 6th months of ART (p<0.001). miR-548ac-3p was upregulated at 6th month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265).Our findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.DiscussionOur findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.
The diagram illustrates the role of circulating miRNAs as determinants of treatment response and prognostic indicators in HIV. It highlights the correlation between miRNA levels, CD4 count, and viral load in both naïve and treated patients, with monitoring intervals at 4, 8, and 24 weeks to assess treatment progress.
Author Tabak, Fehmi
Balkan, Ilker Inanç
Sönmez, Haktan
Umar, Muhammad Ihtisham
Oktan, Burhaneddin
Mete, Bilgül
Küçüksezer, Umut Can
Shahzadi, Andleeb
Deniz, Günnur
AuthorAffiliation 2 Institute of Graduate Studies in Health Sciences, İstanbul University , İstanbul , Türkiye
4 Department of Medical Pharmacology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa , İstanbul , Türkiye
1 Department of Immunology, Aziz Sancar Institute of Experimental Medicine, İstanbul University , İstanbul , Türkiye
3 Department of Infectious Diseases and Clinical Microbiology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa , İstanbul , Türkiye
5 Department of Pharmacy, COMSATS University Islamabad , Lahore , Pakistan
AuthorAffiliation_xml – name: 3 Department of Infectious Diseases and Clinical Microbiology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa , İstanbul , Türkiye
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– name: 4 Department of Medical Pharmacology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa , İstanbul , Türkiye
– name: 1 Department of Immunology, Aziz Sancar Institute of Experimental Medicine, İstanbul University , İstanbul , Türkiye
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Keywords prognostic biomarkers
MicroRNAs (miRNAs)
Human Immunodeficiency Virus (HIV)
Antiretroviral Therapy (ART)
miR-3163 expression
CD4 T-lymphocyte count
quantitative RT-PCR (qRT-PCR)
Language English
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Zhenglin Zhu, Chongqing University, China
Padma Malini Ravi, Agricultural Research Organization (ARO), Israel
These authors have contributed equally to this work
Edited by: Shailendra Saxena, King George’s Medical University, India
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Snippet MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus...
The diagram illustrates the role of circulating miRNAs as determinants of treatment response and prognostic indicators in HIV. It highlights the correlation...
IntroductionMicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human...
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StartPage 1565068
SubjectTerms Adult
Antiretroviral Therapy (ART)
Biomarkers - blood
CD4 Lymphocyte Count
CD4 T-lymphocyte count
Female
HIV Infections - blood
HIV Infections - diagnosis
HIV Infections - drug therapy
HIV Infections - genetics
HIV Infections - immunology
HIV Infections - virology
Human Immunodeficiency Virus (HIV)
Humans
Immunology
Longitudinal Studies
Male
MicroRNAs (miRNAs)
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miR-3163 expression
Prognosis
prognostic biomarkers
Viral Load
Title Longitudinal analysis of hsa-miR-3163, hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-27a-3p as prognostic biomarkers in HIV-infected patients
URI https://www.ncbi.nlm.nih.gov/pubmed/40396180
https://www.proquest.com/docview/3206239307
https://pubmed.ncbi.nlm.nih.gov/PMC12089146
https://doaj.org/article/8722c4bc032f49eea88c41e3b9172e2c
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